A research program in synthetic organic chemistry is described. The proposed research will culminate in the total synthesis of the antitumor alkaloid indicine N-oxide (NSC-132319), via esterification of synthetic retronecine with trachelanthic acid. Total syntheses of heliotridine,lycoricidine, and narciclasine will also result. Lycoricidine and narciclasine both display antitumor activity, and narciclasine has been shown to inhibit protein synthesis in rabbit reticulocytes by 70% at only 10-7 M. Modifications and analogues of all materials will be prepared and subjected to bioassay. All primary synthetic approaches to these four naturally occurring alkaloids utilize as a key step the intramolecular Diels-Alder cycloadditions of acyl nitroso compounds. The development of this chemistry to provide a new, generally useful contribution to the synthetic methodology available for alkaloid synthesis is emphasized. An alternative, or "back-up" synthesis which does not rely on the intramolecular cycloaddition is provided for each compound of interest. Furthermore, back-up approaches to key intermediates for the cycloaddition approach are briefly considered. Funds are requested to support one research assistant and one postdoctoral associate, to provide routine equipment and expendable supplies for the research, and for a limited amount of more permanent chromatographic equipment.